Efficient gene delivery into Epstein-Barr virus (EBV)-transformed human B cells mediated by replication-defective herpes simplex virus-1 (HSV-1): A gene therapy model for EBV-related B cell malignancy

Toshiya Suzuki, Alain Piche, Keizo Kasono, Jialing Xiang, Jesus Gomez-Navarro, Shusuke Moriuchi, David M. Krisky, Thomas Oligino, Joseph C. Glorioso, Tyler J. Curiel, David T. Curiel

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Subgroups of the B cell malignancies are known to be associated with Epstein-Barr virus (EBV) infection, especially in immunocompromised patients. These are fatal and refractory to conventional antineoplastic therapy. B cells are usually post-mitotic cells and even mitogen activated or transformed B cells have shown relative resistance against viral mediated gene transfer. To address this issue, we employed a replication-defective herpes simplex virus-1 (HSV-1) to mediate gene transfer into EBV-transformed B cells. The virus expresses the herpes simplex virus thymidine kinase (HSV-TK) and the E. coli lacZ reporter genes and is designated TOZ.1. We used the lymphoblastoid cell line SWEIG as a model for human EBV-related B cell malignancy. This cell line was established by in vitro EBV infection of primary human peripheral blood mononuclear cells. When SWEIG cells were infected with TOZ.1, X-gal staining revealed lacZ expression in more than 20% cells even at multiplicity of infection (MOI) as low as 1 and the expression persisted for at least one week. Ganciclovir (GCV) administration after TOZ.1 infection effectively decreased the number of the infected tumor cells in a dose-responsive manner. Viral toxicity was analyzed by cell proliferation assay (MTS assay) and found to be little even at 10 MOI infection. Three MOI of the virus yielded maximum antineoplastic effect and more than 50% tumor cells were killed by HSV-TK/GCV. These results suggest the potential utility of replication-defective HSV-1 for the treatment of EBV-related B cell malignancies.

Original languageEnglish
Pages (from-to)686-690
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume252
Issue number3
DOIs
StatePublished - Nov 27 1998
Externally publishedYes

Fingerprint Dive into the research topics of 'Efficient gene delivery into Epstein-Barr virus (EBV)-transformed human B cells mediated by replication-defective herpes simplex virus-1 (HSV-1): A gene therapy model for EBV-related B cell malignancy'. Together they form a unique fingerprint.

Cite this